Triethylamine → HCID 67345283, compound

HRID 1669463Notes

Reaction equation

HRID 1669463 reaction equation
C(O[CH2:9][CH2:10][O:11][CH2:12][CH2:13][N:14]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C@@H:15]1[CH2:22][N:21]2[C:23]3[CH:24]=[C:25]([C:36]([O:38][CH3:39])=[O:37])[CH:26]=[CH:27][C:28]=3[C:29](C3CCCCC3)=[C:20]2[C:19]2[CH:40]=[CH:41][CH:42]=[CH:43][C:18]=2[O:17][CH2:16]1)C1C=CC=CC=1.CS(Cl)(=O)=O.CCN([CH2:61][CH3:62])CC.S([O-])(=O)(=O)C.[CH3:68][NH2:69].[CH2:70]1[CH2:74]O[CH2:72][CH2:71]1>CO.CC(O)=O.[Pd].CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:47]([O:46][C:44]([N:14]([CH2:13][CH2:12][O:11][CH2:10][CH2:9][NH:69][CH3:68])[C@@H:15]1[CH2:22][N:21]2[C:23]3[CH:24]=[C:25]([C:36]([O:38][CH3:39])=[O:37])[CH:26]=[CH:27][C:28]=3[C:29]([CH:62]3[CH2:61][CH2:74][CH2:70][CH2:71][CH2:72]3)=[C:20]2[C:19]2[CH:40]=[CH:41][CH:42]=[CH:43][C:18]=2[O:17][CH2:16]1)=[O:45])([CH3:50])([CH3:49])[CH3:48]

Participants

10

Reactant 5

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 66615946Methylamine tetrahydrofuranHCID 67345671HCID 67345671, compound

Product 1

HCID 67345283HCID 67345283, compoundYield 70%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 23938PalladiumCatalystHCID 6344DichloromethaneSolventHCID 10129899Acetic acid methanolSolvent

Procedure

Methyl (7R)-7-[{2-[2-(benzyloxy)ethoxy]ethyl}(tert-butoxycarbonyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate was dissolved in MeOH/AcOH 10:1 (0.06M) and palladium on carbon (10%, 0.25 eq) was added. The mixture was degassed and hydrogen atmosphere was applied. The mixture was left stirring at RT. After 2 days all volatiles were evaporated in vacuo and the residue was filtered on celite using EtOAc and MeOH as solvents. After evaporation of the solvents in vacuo methyl (7R)-7-{(tert-butoxycarbonyl)[2-(2-hydroxyethoxy)ethyl]amino}-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate was obtained. DMAP (0.2 eq) and MsCl (1.2 eq) was added to a 0.06M solution of previous crude and NEt3 (1.5 eq)) in dry DCM and the mixture was stirred at RT for 90 min. After quenching with sat NaHCO3 the mixture was extracted with DCM and the combined organic phases washed with 1N HCl and brine, dried and concentrated. A 0.07M solution of crude mesylate and NEt3 (4 eq) was treated with 2M MeNH2/THF (22 eq) at 80° C. overnight, evaporation gave a residue that was used as such. Yield 70% (three steps). (ES+) m/z 606 (M+H)+.

Workup

  1. customThe mixture was degassed
  2. waitThe mixture was left
  3. customAfter 2 days all volatiles were evaporated in vacuo
  4. filtrationthe residue was filtered on celite
  5. customAfter evaporation of the solvents in vacuo methyl (7R)-7-{(tert-butoxycarbonyl)[2-(2-hydroxyethoxy)ethyl]amino}-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate
  6. customwas obtained
  7. stirringthe mixture was stirred at RT for 90 min
  8. customAfter quenching with sat NaHCO3 the mixture
  9. extractionwas extracted with DCM
  10. washthe combined organic phases washed with 1N HCl and brine
  11. customdried
  12. concentrationconcentrated
  13. customevaporation
  14. customgave a residue that

Sources & evidence

ORD record
ord-7320e3c27ec942e19e4373c5635a54d7
Source dataset
uspto-grants-2011_08
Patent number
US07989438B2

Reaction notes

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